FGF23: A Review of Its Role in Mineral Metabolism and Renal and Cardiovascular Disease

Abstract

FGF23 is a hormone secreted mainly by osteocytes and osteoblasts in bone. Its pivotal role concerns the maintenance of mineral ion homeostasis. It has been confirmed that phosphate and vitamin D metabolisms are related to the effect of FGF23 and its excess or deficiency leads to various hereditary diseases. Multiple studies have shown that FGF23 level increases in the very early stages of chronic kidney disease (CKD), and its concentration may also be highly associated with cardiac complications. The present review is limited to some of the most important aspects of calcium and phosphate metabolism. It discusses the role of FGF23, which is considered an early and sensitive marker for CKD-related bone disease but also as a novel and potent cardiovascular risk factor. Furthermore, this review gives particular attention to the reliability of FGF23 measurement and various confounding factors that may impact on the clinical utility of FGF23. Finally, this review elaborates on the clinical usefulness of FGF23 and evaluates whether FGF23 may be considered a therapeutic target.

Osteoporosis, an Inevitable Circumstance of Chronic Kidney Disease: A Systematic Review

“…Fibroblast growth factor and klotho: FGF is a polypeptide growth factor [27,28] and a phosphotrophic hormone produced by osteoblasts and osteocytes [28][29][30]. Its biosynthesis is positively regulated by high plasma phosphate and PTH.…”

“…Its biosynthesis is positively regulated by high plasma phosphate and PTH. Bioactive FGF-23 acts on the kidney and parathyroid gland and maintains the homeostasis of its regulators via binding to FGF receptor-1 (FGFR1) [27,28]. However, the interaction between FGF-23 and FGFR1 is weak; hence, the coreceptor klotho increases FGF-23 affinity to its receptor [27].…”

“…Bioactive FGF-23 acts on the kidney and parathyroid gland and maintains the homeostasis of its regulators via binding to FGF receptor-1 (FGFR1) [27,28]. However, the interaction between FGF-23 and FGFR1 is weak; hence, the coreceptor klotho increases FGF-23 affinity to its receptor [27]. Klotho is a pleiotropic protein involved in the inhibition of fibrosis, cellular aging, and apoptosis [27,30].…”

“…However, the interaction between FGF-23 and FGFR1 is weak; hence, the coreceptor klotho increases FGF-23 affinity to its receptor [27]. Klotho is a pleiotropic protein involved in the inhibition of fibrosis, cellular aging, and apoptosis [27,30]. FGF-23, along with klotho, plays a vital role in mineral and hormone homeostasis, bone health, and mineralization [29].…”

“…In the kidney, the interaction between FGF-23 and FGFR1/klotho complex results in decreased phosphate reabsorption by internalization and degradation of the sodium-phosphate cotransporter. It suppresses the formation of vitamin D by reducing the expression of 1α hydroxylase and increases calcium reabsorption in the distal tubule by upregulating calcium-selective channel proteins [27,28,30]. FGF-23 also decreases PTH secretion by inhibiting its gene expression [27,28].…”